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[Preprint]. 2021 Dec 30:2021.12.25.21268211.
doi: 10.1101/2021.12.25.21268211.

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Julie Boucau  1 , Kara W Chew  2 , Manish Choudhary  3 , Rinki Deo  3 , James Regan  3 , James P Flynn  3 , Charles R Crain  3 , Michael D Hughes  4 , Justin Ritz  4 , Carlee Moser  4 , Joan A Dragavon  5 , Arzhang C Javan  6 , Ajay Nirula  7 , Paul Klekotka  7 , Alexander L Greninger  5 , Robert W Coombs  5 , William A Fischer 2nd  8 , Eric S Daar  9 , David A Wohl  8 , Joseph J Eron  8 , Judith S Currier  2 , Davey M Smith  10 , Jonathan Z Li  3 , Amy K Barczak  1   11 ; ACTIV-2/A5401 Study Team
Affiliations

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Julie Boucau et al. medRxiv. .

Update in

  • Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection.
    Boucau J, Chew KW, Choudhary MC, Deo R, Regan J, Flynn JP, Crain CR, Hughes MD, Ritz J, Moser C, Dragavon JA, Javan AC, Nirula A, Klekotka P, Greninger AL, Coombs RW, Fischer WA 2nd, Daar ES, Wohl DA, Eron JJ, Currier JS, Smith DM; POSITIVES study team; Li JZ, Barczak AK; ACTIV-2/A5401 Study Team. Boucau J, et al. Cell Rep Med. 2022 Jul 19;3(7):100678. doi: 10.1016/j.xcrm.2022.100678. Epub 2022 Jun 20. Cell Rep Med. 2022. PMID: 35793677 Free PMC article. Clinical Trial.

Abstract

Monoclonal antibodies (mAbs) are the treatment of choice for high-risk ambulatory persons with mild to moderate COVID-19. We studied viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial. Viral load by qPCR and viral culture were performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAb resulted in rapid clearance of culturable virus in participants without treatment-emergent resistance. One day after treatment, 0 of 28 (0%) participants receiving mAb and 16 of 39 (41%) receiving placebo still had culturable virus (p <0.0001); nasal viral loads were only modestly lower in the mAb-treated group at days 2 and 3. Recrudescence of culturable virus was detected in three participants with emerging mAb resistance and viral load rebound. The rapid reduction in shedding of viable SARS-CoV-2 after mAb treatment highlights the potential role of mAbs in preventing disease transmission.

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Figures

Figure 1.
Figure 1.. Bamlanivimab treatment results in rapid SARS-CoV-2 culture conversion.
(A) Pre-treatment culture positivity and viral load (B) Pre-treatment TCID50 values vs. viral load; TCID50 could only be calculated for participants with ⩾ 3 wells showing CPE. Spearman correlations: placebo r = 0.8482, p-value < 0.0001; Bam mAb r = .6365, p-value = 0.0011. (C) Decay in qPCR-determined viral load over time post-treatment (D) Culture positivity and viral load over time post-treatment. Cx, culture. Bam mAb, bamlanivimab monoclonal antibody.
Figure 2.
Figure 2.. Emergence of bamlanivimab resistance mutations correlates with recrudescent shedding of culturable virus.
(A) Viral load and culture positivity at baseline and day 1 post-treatment for four study participants with recrudescent shedding of culturable virus. Cx, culture (B-E) Viral load and TCID50 for four study participants whose infecting virus developed E484 mutations of the spike protein following bamlanivimab monotherapy.
See this image and copyright information in PMC

References

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